TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22760	68503;68504;68505	chr2:178578662;178578661;178578660	chr2:179443389;179443388;179443387
N2AB	21119	63580;63581;63582	chr2:178578662;178578661;178578660	chr2:179443389;179443388;179443387
N2A	20192	60799;60800;60801	chr2:178578662;178578661;178578660	chr2:179443389;179443388;179443387
N2B	13695	41308;41309;41310	chr2:178578662;178578661;178578660	chr2:179443389;179443388;179443387
Novex-1	13820	41683;41684;41685	chr2:178578662;178578661;178578660	chr2:179443389;179443388;179443387
Novex-2	13887	41884;41885;41886	chr2:178578662;178578661;178578660	chr2:179443389;179443388;179443387
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Fn3-53
• Domain position: 18
• Structural Position: 20
• Q(SASA): 0.1063
• Predicted PPI site: N

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
V/I	None	None	0.78	N	0.588	0.174	0.454054078574	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
V/L	None	None	0.78	N	0.562	0.199	0.393159880135	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
V/A	0.2779	likely_benign	0.2542	benign	-2.225	Highly Destabilizing	0.011	N	0.29	neutral	N	0.494028648	None	None	N
V/C	0.7661	likely_pathogenic	0.7271	pathogenic	-2.149	Highly Destabilizing	0.999	D	0.783	deleterious	None	None	None	None	N
V/D	0.9887	likely_pathogenic	0.9887	pathogenic	-2.694	Highly Destabilizing	0.988	D	0.837	deleterious	None	None	None	None	N
V/E	0.9782	likely_pathogenic	0.9787	pathogenic	-2.396	Highly Destabilizing	0.968	D	0.788	deleterious	D	0.524359012	None	None	N
V/F	0.5759	likely_pathogenic	0.5739	pathogenic	-1.349	Destabilizing	0.996	D	0.815	deleterious	None	None	None	None	N
V/G	0.6621	likely_pathogenic	0.6257	pathogenic	-2.844	Highly Destabilizing	0.811	D	0.745	deleterious	N	0.505405383	None	None	N
V/H	0.9895	likely_pathogenic	0.9885	pathogenic	-2.659	Highly Destabilizing	0.999	D	0.809	deleterious	None	None	None	None	N
V/I	0.0879	likely_benign	0.0865	benign	-0.453	Destabilizing	0.78	D	0.588	neutral	N	0.467495408	None	None	N
V/K	0.986	likely_pathogenic	0.9869	pathogenic	-1.779	Destabilizing	0.976	D	0.788	deleterious	None	None	None	None	N
V/L	0.3259	likely_benign	0.3144	benign	-0.453	Destabilizing	0.78	D	0.562	neutral	N	0.48613431	None	None	N
V/M	0.286	likely_benign	0.2706	benign	-0.848	Destabilizing	0.996	D	0.693	prob.neutral	None	None	None	None	N
V/N	0.957	likely_pathogenic	0.9534	pathogenic	-2.344	Highly Destabilizing	0.988	D	0.841	deleterious	None	None	None	None	N
V/P	0.9871	likely_pathogenic	0.9883	pathogenic	-1.02	Destabilizing	0.988	D	0.81	deleterious	None	None	None	None	N
V/Q	0.9648	likely_pathogenic	0.9626	pathogenic	-2.023	Highly Destabilizing	0.988	D	0.808	deleterious	None	None	None	None	N
V/R	0.9711	likely_pathogenic	0.9734	pathogenic	-1.856	Destabilizing	0.988	D	0.841	deleterious	None	None	None	None	N
V/S	0.7052	likely_pathogenic	0.6479	pathogenic	-3.037	Highly Destabilizing	0.851	D	0.734	prob.delet.	None	None	None	None	N
V/T	0.5744	likely_pathogenic	0.5116	ambiguous	-2.557	Highly Destabilizing	0.919	D	0.661	neutral	None	None	None	None	N
V/W	0.9929	likely_pathogenic	0.9921	pathogenic	-1.8	Destabilizing	0.999	D	0.793	deleterious	None	None	None	None	N
V/Y	0.9542	likely_pathogenic	0.9512	pathogenic	-1.446	Destabilizing	0.996	D	0.803	deleterious	None	None	None	None	N

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.